The majority of hydrogels are polymeric with networks consisting of covalently crosslinked natural or synthetic polymers. Against this backdrop, supramolecular hydrogels, whose networks consist of nanofibers formed through self-assembly of small molecules (i.e., hydrogelators), have emerged as promising biomaterials in the past decade. Estroff, L. A.; Hamilton, A. D. Chem. Rev. 2004, 104, 1201; Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133; Kiyonaka, S.; Sada, K.; Yoshimura, I.; Shinkai, S.; Kato, N.; Hamachi, I. Nat. Mater. 2004, 3, 58; Xing, B. G.; Yu, C. W.; Chow, K. H.; Ho, P. L.; Fu, D. G.; Xu, B. J. Am. Chem. Soc. 2002, 124, 14846; Schneider, J. P.; Pochan, D. J.; Ozbas, B.; Rajagopal, K.; Pakstis, L.; Kretsinger, J. J. Am. Chem. Soc. 2002, 124, 15030; Schnepp, Z. A. C.; Gonzalez-McQuire, R.; Mann, S. Adv. Mater. 2006, 18, 1869; Silva, G. A.; Czeisler, C.; Niece, K. L.; Beniash, E.; Harrington, D. A.; Kessler, J. A.; Stupp, S. I. Science 2004, 303, 1352; and Chen, J.; McNeil, A. J. J. Am. Chem. Soc. 2008, 130, 16496. Usually, the change of temperature, pH, or ionic strength can successfully trigger the formation of supramolecular hydrogels. It is, however, more advantageous to use inherent biological processes to create supramolecular hydrogels in vivo or in situ for certain biomedical applications. Hu, B. H.; Messersmith, P. B. J. Am. Chem. Soc. 2003, 125, 14298; Yang, Z. M.; Liang, G. L.; Guo, Z. F.; Guo, Z. H.; Xu, B. Angew. Chem. Intl. Ed. 2007, 46, 8216. By mimicking biomacromolecular self-assembly (e.g., formation of collagen fibrils), the integration of enzymatic reactions with self-assembly of small molecules provides a effective means to form nanofiber network and result in hydrogels under various conditions. Leikina, E.; Mertts, M. V.; Kuznetsova, N.; Leikin, S. Proc. Natl. Acad. Sci., USA 2002, 99, 1314; Toledano, S.; Williams, R. J.; Jayawarna, V.; Ulijn, R. V. J. Am. Chem. Soc. 2006, 128, 1070; Williams, R. J.; Smith, A. M.; Collins, R.; Hodson, N.; Das, A. K.; Ulijn, R. V. Nat. Nanotech. 2009, 4, 19; Yang, Z.; Liang, G.; Xu, B. Acc. Chem. Res. 2008, 41, 315; and Yang, Z. M.; Gu, H. W.; Fu, D. G.; Gao, P.; Lam, J. K.; Xu, B. Adv. Mater. 2004, 16, 1440.
While it is feasible to initiate hydrogelation using an enzyme that converts a precursor into a hydrogelator, most precursors explored so far bear limited biological activities. However, it was recently discovered that the enzyme-triggered formation of molecular nanofibers can inhibit bacteria growth or selectively kill cancer cells in vitro; the mechanisms of these phenomena likely differ significantly from that of well-established antineoplastic agents that mainly exploit high affinity ligand-receptor binding.